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    藤黄健骨胶囊通过MAGUK/NMDAR/CaMKⅡ信号轴对绝经后骨质疏松症钙磷代谢的机制研究

    Study the Mechanism of Tenghuang Jiangu Capsule on Calcium and Phosphorus Metabolism in Postmenopausal Osteoporosis Through MAGUK/NMDAR/CaMKⅡ Signal Axis

      摘要
    • 摘要:
      目的 探讨藤黄健骨胶囊通过膜结合鸟苷酸激酶(membrane-associated guanylate kinase，MAGUK)/N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor，NMDAR)/钙/钙调蛋白依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinase Ⅱ，CaMKⅡ)信号轴对绝经后骨质疏松症(postmenopausal osteoporosis，PMOP)大鼠钙磷代谢的调控机制。
      方法 双侧卵巢摘除构建绝经后骨质疏松症大鼠模型，随机分为模型组、西药对照组、藤黄健骨胶囊治疗组(高、中、低剂量组)，另外设置假手术组，灌胃给药8周后处死各组动物，检测其末次给药后体质量、血清钙(calcium，Ca)、磷(phosphorus，P)含量，HE观察股骨病理形态改变，micro-CT观察股骨组织形态结构，测定骨体积分数(bone volume fraction，BV/TV)、骨小梁数量(number of trabecular bone，Tb.N)、骨小梁厚度(trabecularbone thickness，Tb.Th)和骨小梁分离度(trabecular bone separation，Tb.Sp)，RT-PCR和Western blotting测定各组动物股骨MAGUK、NMDAR、CaMKⅡ的mRNA表达和蛋白表达。
      结果 与模型组相比，藤黄健骨胶囊显著升高PMOP大鼠血清Ca含量、P含量、BV/TV值、Tb.N值、Tb.Th值(P<0.05或P<0.01)，降低末次给药大鼠的体质量和Tb.Sp值(P<0.01)；改善股骨骨微结构损伤和股骨MAGUK、NMDAR、CaMKⅡ mRNA与蛋白表达(P<0.05或P<0.01)。
      结论 藤黄健骨胶囊能够促进PMOP大鼠钙磷代谢，其机制可能与激活MAGUK/NMDAR/CaMKⅡ信号轴有关。

       

      Abstract:
      OBJECTIVE To explore the regulatory mechanism of Tenghuang Jiangu capsule on calcium and phosphorus metabolism in postmenopausal osteoporosis(PMOP) rats through the membrane-associated guanylate kinase(MAGUK)/N-methyl-D-aspartate receptor(NMDAR)/calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) signaling axis.
      METHODS The PMOP rat models were established by bilateral ovariectomy. They were randomly divided into the model group, the western medicine control group and the Tenghuang Jiangu capsule treatment group(high-dose, medium-dose, low-dose), the other rats were sham-operated group. These rats were sacrificed 8 weeks after intragastric administration. The body mass of the last administration, serum calcium(Ca) and phosphorus(P) contents of the rats were detected. The histopathological morphological changes of femur were observed by HE staining. The bone volume fraction(BV/TV), number of trabecular bone(Tb.N), trabecular bone thickness(Tb.Th), and trabecular bone separation(Tb.Sp) of femurs in each group were measured by micro-CT. The mRNA and protein expressions of MAGUK, NMDAR and CaMKⅡ in the femur was detected with RT-PCR and Western blotting.
      RESULTS  Compared with the model group, Tenghuang Jiangu capsule obviously increased the serum contents of Ca and P, BV/TV, Tb.N, Tb.Th(P<0.05 or P<0.01), and significantly decreased the body mass of the last administration and Tb.Sp(P<0.01). It also obviously improved the bone microstructure injury, the mRNA and protein expressions of MAGUK, NMDAR, CaMKⅡ(P<0.05 or P<0.01).
      CONCLUSION Tenghuang Jiangu capsule can promotes calcium and phosphorus metabolism in PMOP rats. The mechanism may be related to the activation of MAGUK/NMDAR/CaMKⅡ signal axis.

       

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